This project proposes to assess the comparative efficacy and side-effects of the combination of amitriptyline and tranylcypromine, with those of either drug used alone, in the treatment of acutely depressed inpatients. Ninety acutely ill, hospitalized patients meeting Research Diagnostic Criteria for major depressive disorder will be randomly assigned to a course of treatment with either amitriptyline up to 300 mg/day, tranylcypromine up to 60 mg/day, or a combination of tranylcypromine up to 30 mg/day and amitriptyline up to 150 mg/day. Treatment will continue until the patient is sufficiently improved for discharge, or for a maximum of four active treatment weeks Drugs will be given on a double-blind basis, with weekly evaluations by Hamilton interview, Brief Psychiatric Rating Scale, Clinical Global Impression, Global Ward Behavior Rating Scale, and Zung Self-Rating Depression Scale. The subjects will also complete side-effect checklists weekly, have vital signs measured daily, EKGs done weekly, and blood drawn weekly for determination of plasma tricyclic levels and platelet MAO activity. Subjects who improve sufficiently for discharge may continue to take study medications at a constant dosage with weekly evaluations on an outpatient basis to complete the four-week course of the study.